HASIL PENELITIAN

PENGARUH PEMBERIAN KONTRASEPSI PROGESTIN INJEKSI

(DMPA) DAN KONTRASEPSI PROGESTIN ORAL (DOP)

TERHADAP GAMBARAN HISTOPATOLOGIS

ENDOMETRIUM UTERUS TIKUS PUTIH

STRAIN WISTAR

Oleh

FRISTCE HAPPY ARMADIVIN

06020053

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN

2011

LEMBAR PENGESAHAAN

LAPORAN HASIL PENELITIAN

Telah disetujui sebagai hasil penelitian

untuk memenuhi persyaratan

Pendidikan Sarjana Fakultas Kedokteran

Universitas Muhammadiyah Malang

12 Maret 2011

Pembimbing I

dr. Kusuma Andriana, Sp. OG.

Pembimbing II

dr. Dian Yuliartha Lestari.

Mengetahui,

Fakultas Kedokteran

Dekan,

dr. Irma Suswati, M.Kes.

Karya Tulis Akhir oleh Fristce Happy Armadivin ini

telah diuji dan dipertahankan di depan Tim Penguji

Pada tanggal : 12 Maret 2011

Tim Penguji

dr. Kusuma Andriana, Sp. OG. , Ketua

dr. Dian Yuliartha Lestari , Anggota

dr. Moch. Ma’roef, Sp. OG. , Anggota

KATA PENGANTAR

Haturan syukur kehadirat Allah SWT yang telah berkehendak mengalirkan

ridhonya sebagai wujud kasih Khaliq terhadap hamba dalam tiap detik waktu

sehingga proses penyelesaian Tugas Akhir berjudul “Pengaruh Pemberian

Kontrasepsi Progestin Injeksi (DMPA) dan Kontrasepsi Progestin Oral (DOP)

Terhadap Gambaran Histopatologis Endometrium Uterus Tikus Putih Strain

Wistar” ini, tidak mendapat rintangan berarti.

Shalawat salam terlimpahkan pada Nabi besar Muhammad Salallahu

Alaihiwassalam atas kemuliaannya menyampaikan petunjuk kebenaran ke semua

umat manusia.

Dalam kesempatan ini penulis hendak menyampaikan terima kasih pada

pihak yang telah memberikan dukungan baik moril maupun materi diantaranya:

1. dr. Irma Suswati, M.Kes selaku Dekan Fakultas Kedokteran Universitas

Muhammadiyah Malang.

2. dr. Kusuma Adriana, Sp.OG selaku pembimbing I yang telah meluangkan

banyak waktu untuk membimbing, mengarahkan, dan mengevaluasi tugas

akhir ini.

3. dr. Dian Yuliartha Lestari selaku pembimbing II yang telah memberikan

masukan serta dengan sabar menelaah ulang hasil pengerjaan penulis dalam

penyelesaian tugas akhir.

4. dr. Moch. Ma’roef, Sp.OG. selaku penguji yang bersedia meluangkan waktu

memberikan evaluasi akhir untuk tugas akhir ini.

5. Seluruh pihak yang belum tersebut satu persatu

Sebagaimana layaknya manusia, penulis memahami bahwa bukanlah

mustahil jika pada proses penyusunan tugas akhir ini terdapat kesalahan

penyampaian atau penulisan isinya, maka dari itu penulis berharap atas kritik dan

saran yang dapat membantu pelengkapan & pembenahan kekurangan tersebut.

Semoga segala makna dan pengetahuan yang terdapat didalam tugas akhir ini

bias memberi manfaat bagi para pembaca baik kalangan akademisi, praktisi

kesehatan, maupun khalayak umum.

Malang, 18 januari 2011

Fristce Happy A

ABSTRAK

Armadivin, Fristce H. 2011. Pengaruh Pemberian Kontrasepsi Progestin Injeksi

(DMPA) dan Kontrasepsi Progestin Oral (DOP) Terhadap Gambaran

Histopatologis Endometrium Uterus Tikus Putih (Rattus Norvegicus

Strain Wistar). Karya Tulis Akhir, Fakultas Kedokteran Universitas

Muhammadiyah Malang. Pembimbing: (1) Kusuma Adriana, (2) Dian

Yuliartha Lestari.

Latar Belakang: Alasan utama ketidaklanjutan penggunaan kontrasepsi progestin

sintetik adalah efek sampingnya berupa gangguan pola perdarahan. Efek samping

tersebut diduga terjadi akibat adanya perubahan pada struktur endometrium secara

mikroskopik yang disebabkan kerja progestin sintetik pada uterus dalam

menghasilkan hambatan ovulasi

Tujuan penelitian: untuk membuktikan adanya perbedaan gambaran mikroskopik

endometrium tikus putih (Rattus Norvegicus Strain Wistar) pada penggunaan

kontrasepsi progestin jenis injeksi (DMPA) dan jenis oral (DOP).

Metode Penelitian: Penelitian ini merupakan penelitian eksperimental sebenarnya

”True Experimental Study” dengan rancangan penelitian the post test only control

group design yang menggunakan 27 ekor tikus putih betina dibagi dalam 3

kelompok perlakuan yaitu kelompok kontroll, kelompok dengan perlakuan

DMPA, dan kelompok dengan perlakuan DOP. Pemberian DMPA dilakukan

dengan penginjeksian kebagian paha luar atas tikus sedangkan pemberian DOP

dengan cara menyondekan ke mulut tikus.

Hasi Penelitian: hasil uji One Way ANOVA menunjukkan nilai signifikan (p)

kurang dari 0,05 (p<0,05) yang artinya terdapat perbedaan bermakna gambaran

mikroskopis endometrium berdasar jenis progestin yang diberikan. Hasil uji Post

Hoc juga menunjukka nilai signifikan (p<0,05) sehingga dapat disimpulkan

bahwa perbedaan antar kelompok perlakuan adalah bermakna.

Kesimpulan: ada perbedaan gambaran mikroskopis endometrium tikus putih

(Rattus Norvegicus Strain Wistar) pada pemberiaan DMPA dan DOP.

Kata kunci: progestin sintetik, perubahan gambaran mikroskopis pada uterus,

DMPA, DOP

ABSTRAK

Armadivin, Fristce H. 2011. The impact of Injectable Progestasional

Contraception (DMPA) and Oral Progestasional Contraception (DOP) in

Hystopathologycal Micrograph of White Mouse (Rattus Norvegicus Strain

Wistar) Uterine Endometrium. Final, Medical Faculty of University

Muhammadiyah Malang. Lecturer: (1) Kusuma Adriana, (2) Dian Yuliartha

Lestari.

Background: the mean reason of discontinuation from sintetical progestasional

agent is its primary side effect which manifest as bleeding disturbance. This side

effect is supposed happen result in alteration of microscopical endometrium

structure because the action of sintetical progestine in uterus for an ovulation

inhibition.

Objective: to provide a difference microscopical graph of white mouse (Rattus

Norvegicus Strain Wistar) endomterium in Injectable Progestasional

Contraception (DMPA) and Oral Progestasional Contraception (DOP) usage.

Methode: this study is the ”True Experimental Study” with the post test only

control group design as its method. It’s use 27 female white mouse divide into 3

groups that is: control group, group with DMPA usage, and group with DOP

usage. DMPA is given by injecting this into white mouse outside thigh, whereas

DOP is given orally into white mouse mouth.

Result: One Way ANOVA test result is shown significant value (p) less than 0,05

(p<0,05) that means there’s difference in microscopical graph of white mouse

endometrium depend on kind of progestin used. Post Hoc test is also shown

significant value (p<0,05) so it can be conclude that the difference between three

is significant.

Conclusion: There’s a difference micorscopical graph of white mouse (Rattus

Norvegicus Strain Wistar) endometrium in DMPA and DOP usage.

Keywords: Sintetical progestin, microscopical change in uterus, DMPA, DOP

DAFTAR ISI

Halaman

HALAMAN JUDUL .......................................................................................... i

KATA PENGANTAR ....................................................................................... ii

ABSTRAK ......................................................................................................... iv

ABSTRACT ....................................................................................................... v

DAFTAR ISI ..................................................................................................... vi

DAFTAR TABEL ............................................................................................. xi

DAFTAR GAMBAR ........................................................................................ xii

DAFTAR SINGKATAN ................................................................................... xiii

DAFTAR LAMPIRAN ...................................................................................... xv

BAB 1 PENDAHULUAN ................................................................................ 1

1.1 Latar Belakang ............................................................................... 1

1.2 Rumusan Masalah ........................................................................... 3

1.3 Tujuan dan Manfaat Penelitian ........................................................ 4

1.3.1 Tujuan ..................................................................................... 4

1.3.1.1 Tujuan Umum ............................................................. 4

1.3.1.2 Tujuan Khusus ............................................................ 4

1.3.2 Manfaat ................................................................................... 5

1.3.2.1 Manfaat Akademis ...................................................... 5

1.3.2.2 Manfaat Praktis ........................................................... 5

BAB 2 TINJAUAN PUSTAKA ....................................................................... 6

2.1 Kontrasepsi Hormonal ...................................................................... 6

2.1.1 Definisi Kontrasepsi Hormonal............................................... 6

2.1.2 Jenis-jenis Kontrasepsi Hormonal........................................... 6

2.1.2.1 Berdasarkan Kandungan Hormon ............................... 6

2.1.2.2 Berdasarkan Bentuk Sediaan....................................... 7

2.2 Kontrasepsi Progestin ....................................................................... 8

2.2.1 Jenis-jenis Kontrasepsi Progestin ............................................ 8

2.2.1.1 Kontrasepsi Progestin Oral/Mini Pill .......................... 8

2.2.1.2 Kontrasepsi Progestin Injeksi ...................................... 9

2.1.1.3 Kontrasepsi Progestin Implan .................................... 9

2.3 DMPA .............................................................................................. 9

2.3.1 Definisi ................................................................................... 9

2.3.2 Sejarah .................................................................................... 10

2.3.3 Struktur, Nama dan Sifat Kimia .............................................. 10

2.3.4 Komposisi .............................................................................. 11

2.3.5 Farmakodinamik ..................................................................... 11

2.3.6 Farmakokinetik ....................................................................... 12

2.3.7 Efek Samping .......................................................................... 13

2.3.8 Indikasi dan Kontraindikasi .................................................... 15

2.3.9 Waktu pemakaian .................................................................... 16

2.4 DOP .................................................................................................. 17

2.4.1 Definisi .................................................................................... 17

2.4.2 Struktur, Nama dan Sifat Kimia .............................................. 17

2.4.3 Komposisi .............................................................................. 18

2.4.4 Farmakodinamik ..................................................................... 18

2.4.5 Farmakokinetik ....................................................................... 19

2.4.6 Efek Samping .......................................................................... 20

2.4.7 Indikasi dan Kontraindikasi .................................................... 21

2.4.8 Waktu pemakaian .................................................................... 23

2.5 Progestin Natural (Progesteron) & Progestin Sintetik .................... 23

2.5.1 Definisi Progestin Natural ...................................................... 23

2.5.2 Definisi Progestin Sintetik ...................................................... 23

2.5.3 Klasifikasi Progestin Sintetik .................................................. 23

2.5.4 Farmakodinamik Progestin Sintetik ....................................... 24

2.5.5 Aktivitas Biologis Progestin Sintetik ...................................... 25

2.5.5.1 Mekanisme Progestin Sintetik dalam Menimbulkan

Gangguan Pola Perdarahan ........................................... 28

2.6 Uterus Tikus ..................................................................................... 31

2.6.1 Struktur Anatomi Uterus Tikus ............................................... 31

2.6.2 Struktur Histologis Uterus Tikus ........................................... 32

2.6.3 Siklus Reproduksi Tikus ........................................................ 34

2.6.4 Kontrol Endokrin pada Siklus Estrus ...................................... 35

2.6.5 Perubahan Histologis Uterus Tikus Berdasarkan Siklus

Reproduksi .............................................................................. 39

BAB 3 KERANGKA KONSEP DAN HIPOTESIS ......................................... 45

3.1 Kerangka Konsep ............................................................................ 45

3.2 Hipotesis ........................................................................................... 47

BAB 4 METODOLOGI PENELITIAN............................................................. 48

4.1 Rancangan Penelitian ....................................................................... 48

4.2 Tempat dan Waktu Penelitian .......................................................... 48

4.3 Populasi dan Sampel ........................................................................ 48

4.3.1 Populasi ................................................................................... 48

4.3.2 Sampel ..................................................................................... 48

4.3.3 Estimasi besar sampel ............................................................. 48

4.3.4 Karakteristik sampel................................................................ 49

4.3.4.1 Kriteria Inklusi ............................................................ 49

4.3.4.2 Kriteria Eksklusi.......................................................... 50

4.4 Variabel dan Definisi Operasional ................................................... 50

4.4.1 Variabel ................................................................................... 50

4.4.1.1 Variabel Bebas ............................................................ 50

4.4.1.2 Variabel Tergantung.................................................... 50

4.4.2 Definisi Operasional................................................................ 50

4.5 Bahan dan Alat ................................................................................. 51

4.5.1 Bahan....................................................................................... 51

4.5.1.1 Bahan Perlakuan.......................................................... 51

4.5.1.2 Bahan Pemeliharaan ................................................... 52

4.5.1.3 Bahan Persiapan Pembuatan Preparat ......................... 52

4.5.2 Alat ......................................................................................... 52

4.5.2.1 Alat Pemeliharaan Tikus ............................................. 52

4.5.2.2 Alat Perlakuan ............................................................. 52

4.5.2.3 Alat Pembedahan ........................................................ 52

4.5.2.4 Alat Lain...................................................................... 53

4.6 Alur Penelitian ................................................................................. 54

4.7 Prosedur Penelitian........................................................................... 55

4.7.2 Pembagian Kelompok Tikus ................................................... 55

4.7.2 Adaptasi................................................................................... 55

4.7.3 Sinkronisasi Hormon ............................................................... 55

4.7.4 Pemberian Kontrasepsi Progestin ........................................... 56

4.7.5 Pembuatan Sediaan Histologis ................................................ 58

4.7.6 Perlakuan Terhadap Tikus Setelah Pengambilan Uterus ........ 61

4.7.7 Pengamatan Hasil .................................................................... 61

4.8 Metode Analisis Data ...................................................................... 61

BAB 5 HASIL DAN ANALISIS DATA ........................................................... 62

BAB 6 PEMBAHASAN .................................................................................... 72

BAB 7 PENUTUP.............................................................................................. 77

7.1 Kesimpulan ...................................................................................... 77

7.2 Saran ................................................................................................. 77

DAFTAR PUSTAKA ........................................................................................ 81

LAMPIRAN ....................................................................................................... 85

DAFTAR TABEL

Halaman

2.1 Jenis-jenis mini pill yang beredar di dunia................................................ 8

2.2 Komposisi DMPA ..................................................................................... 11

2.3 Indikasi & Kontraindikasi DMPA ............................................................ 16

2.4 Rekomendasi Waktu Pemakaian DOP ...................................................... 23

2.5 Klasifikasi Progestin & Contoh Senyawanya ........................................... 24

2.6 Afinitas Relatif Ikatan Progesteron & Progestin Sintetik pada Reseptor

Steroid & Protein Serum ........................................................................... 26

2.7 Efektifitas Aktifitas Progestasional dari Beragam Progestin .................... 28

5.1 Gambaran deskriptif sediaan mikroskopis (histopatologis)

endometrium dari masing-masing kelompok perlakuan ........................... 69

5.2 Hasil rerata jumlah eritrosit, jumlah leukosit, ukuran tebal epitel

dan ukuran diameter pembuluh darah per 10 lapang pandang.................. 70

5.3 Hasil rerata jumlah eritrosit, jumlah leukosit, ukuran tebal epitel

dan ukuran diameter pembuluh darah ....................................................... 70

5.4 Rincian nilai Hasil Uji Normalitas (Shapiro Wilk72

5.5 Rincian Nilai Hasil Uji Homogenitas Setelah Data Ditransformasi ......... 72

5.6 Rincian Nilai Hasil Uji Post Hoc Tukey ................................................... 73

DAFTAR GAMBAR

Halaman

2.1 Struktur Kimia Medroxyprogesterone Acetate .................................... 10

2.2 Struktur Kimia Desogestrel.................................................................. 17

2.3 Struktur Anatomi Uterus Tikus ........................................................... 32

2.4 Uterine horn ........................................................................................ 33

2.5 Endometrium ........................................................................................ 33

2.6 Variasi durasi fase-fase siklus etrus ..................................................... 35

2.7 Fluktuasi hormon reproduksi selama siklus estrus .............................. 35

2.8 Interaksi hormonal dari HPO aksis ...................................................... 39

2.9 Uterus pada fase proestrus .................................................................. 41

2.10 Uterus pada fase estrus ...................................................................... 42

2.11 Uterus pada fase metestrus ................................................................ 43

2.12 Uterus pada fase diestrus ................................................................... 44

3.1 Bagan Kerangka Konsep Penelitian ..................................................... 45

4.1 Cara Menghitung Eritrosit dan Leukosit .............................................. 51

4.2 Cara Mengukur Diameter Lumen Pembuluh Darah ............................ 51

4.3 Cara Mengukur Ketebalan Epitel Endometrium .................................. 51

4.4 Bagan Alur Penelitian .......................................................................... 54

DAFTAR SINGKATAN

AR : Androgen receptor

ASI : Air susu ibu

BTB : Breakthrough Bleeding

CBG : Corticosteroid binding globulin

DMPA : Depomedroxyprogesterone acetate

DOP : Desogestrel only pill

ER : Estrogen reseptor

FDA : Food & Drug Administration

FSH : Follicle stimulating hormone

GR : Glucocorticoid receptor

HPO : Hipofisis-pituitary-ovarium

ICAM : Intracellular Adhesion Molecule

IUGR : Intra uterine growth restriction

LH : Luteinizing hormone

LH-RH : Luteinizing hormone-releasing hormone

MMP : Matrix Metalloproteinase

MR : Mineralocorticoid receptor

NET-EN : Norethindrone enanthate

PMN : Polymorphonuclear

PR : Progesterone receptor

RP : Reference periode

SHBG : Sex hormone-binding globulin

TIMP : Tissue Inhibitor Matrix Metalloproteinase

UK : United Kingdom

VO : Vaginal opening

VCAM : Vascular Cell Adhesion Molecule

DAFTAR LAMPIRAN

Halaman

Lampiran 1. Hasil Penghitungan Jumlah Eritrosit Endometrium Tikus .......... 85

Lampiran 2. Hasil Penghitungan Jumlah Leukosit Endometrium Tikus ......... 86

Lampiran 3. Hasil Pengukuran Tebal Epitel Endometrium Tikus ................... 87

Lampiran 4. Hasil Pengukuran Diameter Pembuluh Darah Endometrium

Tikus ........................................................................................... 88

Lampiran 5. Dokumentasi Penelitian ............................................................... 99

Lampiran 6. Kode Etik ..................................................................................... 102

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